title: The food intake-suppressive effects of glucagon-like peptide-1 receptor signaling in the ventral tegmental area are mediated by AMPA/kainate receptors.
abstract: Glucagon-like peptide-1 receptor (GLP-1R) activation in the ventral tegmental area (VTA) is physiologically relevant for the control of palatable food intake. Here, we tested whether the food intake-suppressive effects of VTA GLP-1R activation are mediated by glutamatergic signaling within the VTA. Intra-VTA injections of the GLP-1R agonist exendin-4 (Ex-4) reduced palatable high-fat food intake in rats primarily by reducing meal size; these effects were mediated in part via glutamatergic AMPA/kainate but not NMDA receptor signaling. Additional behavioral data indicated that GLP-1R expressed specifically within the VTA can partially mediate the intake- and body weight-suppressive effects of systemically administered Ex-4, offering the intriguing possibility that this receptor population may be clinically relevant for food intake control. Intra-VTA Ex-4 rapidly increased tyrosine hydroxylase levels within the VTA, suggesting that GLP-1R activation modulates VTA dopaminergic signaling. Further evidence for this hypothesis was provided by electrophysiological data showing that Ex-4 increased the frequency of AMPA-mediated currents and reduced the paired/pulse ratio in VTA dopamine neurons. Together, these data provide novel mechanisms by which GLP-1R agonists in the mesolimbic reward system control for palatable food intake.
authors.affiliation: Translational Neuroscience Program and.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Mietlicki-Baase
authors.forename: Pavel I
authors.initials: PI
authors.lastname: Ortinski
authors.forename: Laura E
authors.initials: LE
authors.lastname: Rupprecht
authors.forename: Diana R
authors.initials: DR
authors.lastname: Olivos
authors.forename: Amber L
authors.initials: AL
authors.lastname: Alhadeff
authors.forename: R Christopher
authors.initials: RC
authors.lastname: Pierce
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hayes
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D001069:Appetite Regulation / Q000187:drug effects*; D059305:Diet, High-Fat; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D018027:Receptors, Glucagon / Q000819:agonists* / Q000502:physiology; D018092:Kainic Acid Receptors / Q000502:physiology*; D012201:Reward; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism
chemical_list: D001067:Appetite Depressants; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D018091:Receptors, AMPA; D018027:Receptors, Glucagon; D018092:Kainic Acid Receptors; C000593835:Glp1r protein, rat
keywords: 2-amino-3-hydroxy-5-methyl-4-isoxazol propionic acid; diabetes; dopamine; glucagon-like peptide-1; glutamate; obesity; reward